Hi, my name is Laya Kumar. I'm fifteen years old and I live in Lexington, Massachusetts. I'm a rising sophomore at Lexington High School. I lived in Birmingham, Michigan till the beginning of my freshman year of high school then I moved to the Boston area. A few of the Earth Science teachers at me school were giving out ideas on camps that would help with our biology classes next year, and this camp has already proved to be an excellent source of information on biology as well as a great learning experience for me and my fellow students.
In sophomore year I'm planning on taking AP Biology, which will be my first biology course. Though I've never taken biology before, I've done some research on genetics before with my dad and the brief time I spent on biology in prior science classes sparked my interest on the subject. Biological Research as well as synthetic biology are new subjects, but they have already proved to be very interesting and I'm looking forward to exploring these fields in the coming weeks.
In freshman year I took Honors Math 2 and Honors Earth Science. Honors Math 2 is a combination of Honors Geometry, Honors Algebra 2, and Honors Statistics. The course itself was fairly challenging but my teacher, Mrs. Lindsay Mosca, made the course very enjoyable. I also enjoyed Earth Science, but am looking forward to a more captivating subject in the sciences next year.
My interests apart from math and science are traveling and international affairs. I joined my schools Model UN team this year, and was immediately interested in foreign affairs. I have gone to a few conferences this year, and took part in hosting a conference at my own school. I am very excited to learn more about foreign affairs, because I believe this subject is extremely important in the world today. Part of my interest in foreign affairs comes from my interest in traveling. I have family all over the world, from London to India to South America. I enjoy visiting them and experiencing other cultures because I feel that learning about how others live is a very important part of life.
AMD is a hereditary ocular disease that is the leading cause for blindness in all Americans above the age of 60. Along with it being one of the leading causes of blindness in this world, it has no cures. AMD progresses in two stages. It starts off as Dry AMD which overtime degenerates the macula by destroying the outsides with lipid deposits called drusen. As the disease progresses, blood vessels above the macula begin to leak and deteriorate the macula even further, ultimately resulting in loss of central vision. Though Dry AMD is the most common stage of the disease, with 85-90% of the people who have AMD experiencing it, Wet AMD does the most damage.
How does Wet AMD work
AMD is a hereditary ocular disease that is the leading cause for blindness in all Americans above the age of 60. There are typically two major types of AMD, wet and dry. Wet AMD is the type this report is focused on, but is typically preceded by Dry AMD. Wet AMD occurs when abnormal blood vessels in the choroid grow and leak into the macula, damaging the macula permanently. The macula is a small, pigmented part of your eye in that surrounds the fovea. The fovea is a small pit that contains the largest amount of rod cells in your eye. The macula is therefore responsible for all central vision in your eye. Both the macula and the fovea are located in the center of the retina, which in turn is located directly under the choroid. The choroid is an area in your eye that transports oxygen to your eye. A part of the choroid called the Bruch’s membrane is typically the area where abnormal growth will occur, and leak directly into the macula.
Wet AMD occurs when the Bruch’s membrane experiences an overproduction of vascular endothelial growth factor (VEGF), a signal molecule that triggers choroidal neovascularization. Choroidal neovascularization is the abnormal growth of blood vessels. As these blood vessels grow in a tight area they begin to hemorrhage, and leak into the macula directly below it.
Effects of Wet AMD
The macula is a very important of the eye. The macula is the part of the eye that has the most cone cells and is therefore responsible for central, high resolution vision. When blood vessels in the choroid hemorrhage and leak into the macula it can cause a subretinal fibrotic scar which could lead to permanent vision loss. Typically, as the macula only affects central vision, but the peripheral vision is working, vision begins to become distorted and blurry in the center, but your sideview is fine.
Current treatments for Wet AMD
Currently there are no cures for Wet AMD, yet there are a few effective treatments. The leading treatment for Wet AMD is Lucentis. Lucentis is the brand name for the drug ranibizumab, which is the only drug powerful enough to stop the damage created by the choroidal neovascularization.
However, Lucentis is deployed through eye injections, and therefore can increase eye pressure and create other discomforts. In addition, Lucentis does not work to strengthen the eye after it takes effect, which will still leave patients with poor eyesight. However, Lucentis is the only medication that stops angiogenesis effectively.
How Ranibizumab Works
Ranibizumab is a monoclonal antibody that has inhibits angiogenesis by inhibiting the signal molecule vascular endothelial growth factor. Ranibizumab binds to the ribosome binding site of active forms of VEGF-A. The binding of ranibizumab prevents VEGF from interacting with its receptors, therefore stopping the creation of the blood vessels.
We Can Treat It But Can’t Cure It
Wet AMD does have an effective treatment, but it does not have a cure. The best way to stop wet AMD is to cure it in it’s early form. Dry AMD always happens before wet AMD, and dry AMD degrades the macula severely. When wet AMD occurs, dry AMD has already degraded the macula to the point that it can’t protect itself from the leakage. Therefore, the best way to stop wet AMD from occurring is to stop dry AMD.
What is Dry AMD?
Dry AMD is the type of AMD that affects nearly 90% of the population. It takes place in the retinal pigment epithelium (RPE), which is right above the macula. It is the part of the macula that also borders the choroid. Typically what happens is RPE cells and photoreceptors begin to die and form clumps. These clumps harden into big, yellow spots on the RPE called drusen. Drusen can cause discomfort to most as these protein deposits tend to cover some RPE cells, preventing the cells from doing their job. This could cause slight loss in vision and blurriness.
The late stage of Dry AMD is called Geographic Atrophy. It is very dangerous to the macula, and could cause permanent loss in vision. The drusen deposits begin to harden on the eye, as the spots grow they rip through active rod and cone cells in your retina, which are responsible for sight. They also rip through the RPE cells throughout the eye. This could cause severe loss of central vision. It could potentially create a scotoma, or a patch of blindness in the center of your eye.
What Causes Drusen?
Drusen is primarily created when degenerated retinal pigment epithelial cells (RPE) and photoreceptors break down into debris and aggregate along the RPE basal folds, little folds that appear throughout the RPE. The RPE is the part of the retina that borders on the choroid, specifically the Bruch’s membrane. As the debris gather on the RPE and begin to block oxygen flow they trigger the immune system, which sends T cells to the eye, inflaming it. The RPE begins to compress the debris which then hardens. Instead of fighting of infection, the eye creates an environment in which drusen can flourish, which severely damages the macula. Overtime these proteins and cells create large, yellow spots in the back of the eye.
The Project:
Background
Docosahexaenoic acid (DHA) combines with an amino acid group called lysyls, creating CEP. CEP is the signal molecule the immune system uses to trigger the T Cells created in thymus.
M1 macrophages are also created in the thymus, and they are sent to the area in which the signal molecule was created. When the T Cells reach the area, they bind with the CEP and release cytokine TSFα which creates inflammation and the macrophages.
Design
My project would use quorum sensing to allow the T Cells to bind with CEP until the amount of cells reach quorum, at which point the bacteria would release an inhibitor called CD47.
My system would potentially be composed of five steps to reach the end result:
Signal molecule CEP would be released throughout the retinal epithelium pigment (REP). This molecule would activate the T cells and M1 macrophages in the thymus, and they would be sent to the REP to attack the molecules they sensed and break down the debris deposits around the CEP. (Not shown on diagram)
The CEP molecules would trigger the T Cells into releasing cytokine TSFα, which would in turn create inflammation throughout the REP and activating the M1 macrophages. However, bacteria using quorum sensing will have been released into the eye, and they would be sensing the amount of T Cells that were in the REP. The bacteria would wait until the cells reach quorum before releasing the inhibitor. This ensures the T Cells will do their job of breaking down drusen, but will not reach the amount which creates enough inflammation for the eye to be a compaction sight.
Once the T Cells reach quorum, the bacteria will release the cluster of differentiation 47. The CD47 is an inhibitor, and will then find the T Cells and bind to them.
The CD47 is a T Cell inhibitor that binds to the TCR (autoreactive T Cell receptor), preventing it from sending the CEP molecules down to the repressor. The T Cell typically uses negative regulation to activate the T Cells. The inhibition of the signal molecule to the repressor will allow the repressor to stay on the promoter, which prevents the cell from expressing the inflammatory cytokines.
As the cell is inhibited and will not send out cytokines, the M1 macrophages will not be expressed.
Prior to inhibitor binding to T Cell
After inhibitor binds to T Cell
Devices needed in order for system to operate:
Bacteria modified to work in the eye with quorum sensing abilities altered to release CD47
Inhibitor modified to inhibit the FoxP3 gene (CD47)
Expected Results:
By regulating the amount of T Cells, and in turn M1 macrophages, the inflammation in the RPE will go down as no more TSFα cytokine will be produced. However, enough T Cells will be allowed into the RPE so that the breakdown of RPE cells and photoreceptors will be allowed. In addition, the deprivation of an inflamed RPE will take away the compaction the cells need to harden into drusen. Drusen will be unable to form, leaving the macula intact and protected, guarding the fovea as well. This not only cures Dry AMD, but Wet AMD as well. The macula will no longer be degraded, so leakage from hemorrhaged blood vessels in the choroid will not impact the macula nearly as much. This system combined with Lucentis will allow the macula to remain safe and secure throughout the lives of the infected people.
Advantages:
At this point in time there are no known treatments for Dry AMD. This is well worth the funding as more than 2 million people across the US suffer from Dry and Wet AMD.
Potential Problems:
This design has three major potential problems:
Patient Safety: Quorum sensing technology is based off of bacteria sensing the amount of other cells around them through their signal molecules, and once the amount of cells reach a certain number, the bacteria come to quorum. However, this is only a common trait in bacteria. Putting foreign bacteria in the eye is a very risky proposition, and could result in serious side effects. One way around this is figuring out a way for other types of cells to imitate the quorum sensing behavior. Another is finding bacteria native to the eye to use when deploying this device.
Deployment: It is now known how to create a system in which we can de-inflame the retina. Even so, we do not yet know how to deploy said system into the eye. There are a few possibilities in deploying this system. An ocular injection is one possibility to inserting the proteins needed, but ocular injections are known to have serious side effects such as pressurization of the eye, causing further diseases. Another possibility is injecting it in your arm and allow it to flow through the bloodstream. However this could affect the optic nerve, and damage vision.
Unknowns: Like all genetic experiments, this system has the ability to mutate into something that was completely unexpected. Although this is a problem in all genetic experiments, it is still a concern that needs to be addressed. All biologists and engineers would be following safety guidelines given to them, but there is always a chance something could go wrong. This is also true in the eye. We do not know the reaction of many of these devices in the eye, so we can never be sure how this will work.
Testing:
I would test this system by deploying the inhibitors in the eye and checking for inflammation throughout the retina. The best way to test this would be on rats, as both types of AMD have been replicated by scientists already. If the retina of the rat swells, the test did not work. It is always good to test a system before deploying it, and I recommend that this is tested several times on several people before it is even thought of as a legitimate cure.
In sophomore year I'm planning on taking AP Biology, which will be my first biology course. Though I've never taken biology before, I've done some research on genetics before with my dad and the brief time I spent on biology in prior science classes sparked my interest on the subject. Biological Research as well as synthetic biology are new subjects, but they have already proved to be very interesting and I'm looking forward to exploring these fields in the coming weeks.
In freshman year I took Honors Math 2 and Honors Earth Science. Honors Math 2 is a combination of Honors Geometry, Honors Algebra 2, and Honors Statistics. The course itself was fairly challenging but my teacher, Mrs. Lindsay Mosca, made the course very enjoyable. I also enjoyed Earth Science, but am looking forward to a more captivating subject in the sciences next year.
My interests apart from math and science are traveling and international affairs. I joined my schools Model UN team this year, and was immediately interested in foreign affairs. I have gone to a few conferences this year, and took part in hosting a conference at my own school. I am very excited to learn more about foreign affairs, because I believe this subject is extremely important in the world today. Part of my interest in foreign affairs comes from my interest in traveling. I have family all over the world, from London to India to South America. I enjoy visiting them and experiencing other cultures because I feel that learning about how others live is a very important part of life.
___
Presentation
Age Related Macular Degeneration
What is AMD
AMD is a hereditary ocular disease that is the leading cause for blindness in all Americans above the age of 60. Along with it being one of the leading causes of blindness in this world, it has no cures. AMD progresses in two stages. It starts off as Dry AMD which overtime degenerates the macula by destroying the outsides with lipid deposits called drusen. As the disease progresses, blood vessels above the macula begin to leak and deteriorate the macula even further, ultimately resulting in loss of central vision. Though Dry AMD is the most common stage of the disease, with 85-90% of the people who have AMD experiencing it, Wet AMD does the most damage.How does Wet AMD work
AMD is a hereditary ocular disease that is the leading cause for blindness in all Americans above the age of 60. There are typically two major types of AMD, wet and dry. Wet AMD is the type this report is focused on, but is typically preceded by Dry AMD. Wet AMD occurs when abnormal blood vessels in the choroid grow and leak into the macula, damaging the macula permanently. The macula is a small, pigmented part of your eye in that surrounds the fovea. The fovea is a small pit that contains the largest amount of rod cells in your eye. The macula is therefore responsible for all central vision in your eye. Both the macula and the fovea are located in the center of the retina, which in turn is located directly under the choroid. The choroid is an area in your eye that transports oxygen to your eye. A part of the choroid called the Bruch’s membrane is typically the area where abnormal growth will occur, and leak directly into the macula.Wet AMD occurs when the Bruch’s membrane experiences an overproduction of vascular endothelial growth factor (VEGF), a signal molecule that triggers choroidal neovascularization. Choroidal neovascularization is the abnormal growth of blood vessels. As these blood vessels grow in a tight area they begin to hemorrhage, and leak into the macula directly below it.
Effects of Wet AMD
The macula is a very important of the eye. The macula is the part of the eye that has the most cone cells and is therefore responsible for central, high resolution vision. When blood vessels in the choroid hemorrhage and leak into the macula it can cause a subretinal fibrotic scar which could lead to permanent vision loss. Typically, as the macula only affects central vision, but the peripheral vision is working, vision begins to become distorted and blurry in the center, but your sideview is fine.
Current treatments for Wet AMD
Currently there are no cures for Wet AMD, yet there are a few effective treatments. The leading treatment for Wet AMD is Lucentis. Lucentis is the brand name for the drug ranibizumab, which is the only drug powerful enough to stop the damage created by the choroidal neovascularization.
However, Lucentis is deployed through eye injections, and therefore can increase eye pressure and create other discomforts. In addition, Lucentis does not work to strengthen the eye after it takes effect, which will still leave patients with poor eyesight. However, Lucentis is the only medication that stops angiogenesis effectively.How Ranibizumab Works
Ranibizumab is a monoclonal antibody that has inhibits angiogenesis by inhibiting the signal molecule vascular endothelial growth factor. Ranibizumab binds to the ribosome binding site of active forms of VEGF-A. The binding of ranibizumab prevents VEGF from interacting with its receptors, therefore stopping the creation of the blood vessels.We Can Treat It But Can’t Cure It
Wet AMD does have an effective treatment, but it does not have a cure. The best way to stop wet AMD is to cure it in it’s early form. Dry AMD always happens before wet AMD, and dry AMD degrades the macula severely. When wet AMD occurs, dry AMD has already degraded the macula to the point that it can’t protect itself from the leakage. Therefore, the best way to stop wet AMD from occurring is to stop dry AMD.What is Dry AMD?
Dry AMD is the type of AMD that affects nearly 90% of the population. It takes place in the retinal pigment epithelium (RPE), which is right above the macula. It is the part of the macula that also borders the choroid. Typically what happens is RPE cells and photoreceptors begin to die and form clumps. These clumps harden into big, yellow spots on the RPE called drusen. Drusen can cause discomfort to most as these protein deposits tend to cover some RPE cells, preventing the cells from doing their job. This could cause slight loss in vision and blurriness.
The late stage of Dry AMD is called Geographic Atrophy. It is very dangerous to the macula, and could cause permanent loss in vision. The drusen deposits begin to harden on the eye, as the spots grow they rip through active rod and cone cells in your retina, which are responsible for sight. They also rip through the RPE cells throughout the eye. This could cause severe loss of central vision. It could potentially create a scotoma, or a patch of blindness in the center of your eye.
What Causes Drusen?
Drusen is primarily created when degenerated retinal pigment epithelial cells (RPE) and photoreceptors break down into debris and aggregate along the RPE basal folds, little folds that appear throughout the RPE. The RPE is the part of the retina that borders on the choroid, specifically the Bruch’s membrane. As the debris gather on the RPE and begin to block oxygen flow they trigger the immune system, which sends T cells to the eye, inflaming it. The RPE begins to compress the debris which then hardens. Instead of fighting of infection, the eye creates an environment in which drusen can flourish, which severely damages the macula. Overtime these proteins and cells create large, yellow spots in the back of the eye.The Project:
Background
Docosahexaenoic acid (DHA) combines with an amino acid group called lysyls, creating CEP. CEP is the signal molecule the immune system uses to trigger the T Cells created in thymus.
M1 macrophages are also created in the thymus, and they are sent to the area in which the signal molecule was created. When the T Cells reach the area, they bind with the CEP and release cytokine TSFα which creates inflammation and the macrophages.Design
My project would use quorum sensing to allow the T Cells to bind with CEP until the amount of cells reach quorum, at which point the bacteria would release an inhibitor called CD47.
My system would potentially be composed of five steps to reach the end result:
Prior to inhibitor binding to T Cell
After inhibitor binds to T Cell
Devices needed in order for system to operate:Expected Results:
By regulating the amount of T Cells, and in turn M1 macrophages, the inflammation in the RPE will go down as no more TSFα cytokine will be produced. However, enough T Cells will be allowed into the RPE so that the breakdown of RPE cells and photoreceptors will be allowed. In addition, the deprivation of an inflamed RPE will take away the compaction the cells need to harden into drusen. Drusen will be unable to form, leaving the macula intact and protected, guarding the fovea as well. This not only cures Dry AMD, but Wet AMD as well. The macula will no longer be degraded, so leakage from hemorrhaged blood vessels in the choroid will not impact the macula nearly as much. This system combined with Lucentis will allow the macula to remain safe and secure throughout the lives of the infected people.Advantages:
At this point in time there are no known treatments for Dry AMD. This is well worth the funding as more than 2 million people across the US suffer from Dry and Wet AMD.Potential Problems:
This design has three major potential problems:Testing:
I would test this system by deploying the inhibitors in the eye and checking for inflammation throughout the retina. The best way to test this would be on rats, as both types of AMD have been replicated by scientists already. If the retina of the rat swells, the test did not work. It is always good to test a system before deploying it, and I recommend that this is tested several times on several people before it is even thought of as a legitimate cure.Sources:
Pictures:
https://www.pinterest.com/pin/229472543489256603/
http://www.familyhealthonline.ca/fho/growingolder/_images/GO_macular_dia2.jpg
https://courses.cit.cornell.edu/psych431_nbb421/student2006/mpl33/dryAMD_files/image004.jpg
http://blog.scratchmenot.com/wp-content/uploads/2012/09/eye-drops-300x300.jpg
http://www.woodlandsretina.com/s/cc_images/cache_3027049004.png?t=1304944314
http://www.sciencedirect.com/science/article/pii/S0002939402016240
http://www.lucentis.com/sites/lucentis.com/files/img/slide-lucentis-help.png
Anti Inflammatory Stuff -
http://www.ncbi.nlm.nih.gov/pubmed/20303874
T Cells -
http://www.jimmunol.org/content/178/9/5930.short
Signal Molecules:
http://www.nature.com/nm/journal/v14/n2/full/nm1709.html
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3844284/
Inhibitors:
http://pathology.wustl.edu/training/advdocs/2010/Schreiber%20Adv%20Topics%202010.pdf